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Int. J. Mol. Sci. 2014, 15(12), 22173-22187; doi:10.3390/ijms151222173

Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease

1
Grup de Recerca GEMMAIR (AGAUR)-Medicina Aplicada, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), Institut d'Investigació Sanitària Pere Virgili IISPV (IISPV), Tarragona 43003, Spain
2
Servei Medicina Interna, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain
3
Servei Anatomia Patològica, Hospital Universitari Joan XXIII Tarragona, Mallafré Guasch, 4, Tarragona 43007, Spain
4
Servei de Cirurgia, Hospital Sant Joan de Reus, Departament de Medicina i Cirurgia, Universitat Rovira i Virgili (URV), IISPV, Avinguda Doctor Josep Laporte, 2, Tarragona 43204, Spain
These authors contributed equally to this work.
*
Author to whom correspondence should be addressed.
Received: 2 October 2014 / Revised: 25 November 2014 / Accepted: 25 November 2014 / Published: 2 December 2014
(This article belongs to the Collection Molecular Mechanisms of Human Liver Diseases)
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Abstract

Lipid accumulation in the human liver seems to be a crucial mechanism in the pathogenesis and the progression of non-alcoholic fatty liver disease (NAFLD). We aimed to evaluate gene expression of different fatty acid (FA) metabolism-related genes in morbidly obese (MO) women with NAFLD. Liver expression of key genes related to de novo FA synthesis (LXRα, SREBP1c, ACC1, FAS), FA uptake and transport (PPARγ, CD36, FABP4), FA oxidation (PPARα), and inflammation (IL6, TNFα, CRP, PPARδ) were assessed by RT-qPCR in 127 MO women with normal liver histology (NL, n = 13), simple steatosis (SS, n = 47) and non-alcoholic steatohepatitis (NASH, n = 67). Liver FAS mRNA expression was significantly higher in MO NAFLD women with both SS and NASH compared to those with NL (p = 0.003, p = 0.010, respectively). Hepatic IL6 and TNFα mRNA expression was higher in NASH than in SS subjects (p = 0.033, p = 0.050, respectively). Interestingly, LXRα, ACC1 and FAS expression had an inverse relation with the grade of steatosis. These results were confirmed by western blot analysis. In conclusion, our results indicate that lipogenesis seems to be downregulated in advanced stages of SS, suggesting that, in this type of extreme obesity, the deregulation of the lipogenic pathway might be associated with the severity of steatosis. View Full-Text
Keywords: insulin resistance; morbid obesity; fatty acid metabolism; non-alcoholic fatty liver disease; simple steatosis; non-alcoholic steatohepatitis insulin resistance; morbid obesity; fatty acid metabolism; non-alcoholic fatty liver disease; simple steatosis; non-alcoholic steatohepatitis
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Auguet, T.; Berlanga, A.; Guiu-Jurado, E.; Martinez, S.; Porras, J.A.; Aragonès, G.; Sabench, F.; Hernandez, M.; Aguilar, C.; Sirvent, J.J.; Del Castillo, D.; Richart, C. Altered Fatty Acid Metabolism-Related Gene Expression in Liver from Morbidly Obese Women with Non-Alcoholic Fatty Liver Disease. Int. J. Mol. Sci. 2014, 15, 22173-22187.

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